Editors' ChoiceCancer

Epidermal Growth Factor Receptor: Not Just Epidermal

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Science Translational Medicine  20 Oct 2010:
Vol. 2, Issue 54, pp. 54ec163
DOI: 10.1126/scitranslmed.3001791

Bone marrow transplantation is a potentially life-saving technique in which hematopoietic stem and progenitor cells (HSPCs) are injected into a patient to rescue bone marrow failure. Bone marrow transplantation is commonly performed in patients with nonmalignant conditions such as aplastic anemia as well as cancers such as leukemia or lymphoma. Granulocyte colony–stimulating factor (G-CSF) treatment causes HSPCs to enter into the circulation, where they can be easily collected; however, individuals are highly variable in their ability to mobilize HSPCs, with up to 10% of individuals failing to mobilize sufficient numbers of HSPCs for transplantation. This variability is also seen in mice, where one mouse strain mobilizes 10-fold more HSPCs than another. Ryan and colleagues previously showed that this disparity mapped to a region on chromosome 11. They generated mice in which the chromosome 11 region was the only region from the “good mobilizer” strain, and these mice retained their high mobilization capacity. Mice that were transplanted with HSPCs from the good-mobilizer strain retained the ability to mobilize high numbers of HSPCs, suggesting that the gene on chromosome 11 acts in HSPCs directly and not in the surrounding stroma.

The authors now identify the gene on chromosome 11 responsible for the “good-mobilizer” phenotype as epidermal growth factor receptor (EGFR), which was previously not suspected of having a role in HSPCs. EGFR expression varies between individuals because of several polymorphisms. The poor-mobilizer mice had high levels of EGFR, suggesting that it is a negative regulator of HSPC mobilization. Indeed, mice treated with EGF had reduced mobilization, whereas mice carrying an inactivating mutation in one EGFR allele had higher mobilization capacity, as did mice treated with erlotinib, which is an EGFR inhibitor. Thus, this study provides a rationale for exploring the use of erlontinib to enhance G-CSF–induced HSPC mobilization in patients. Moreover, although EGFR may not be the only gene on chromosome 11 responsible for variation in HSPC mobilization capacity, it may be worth exploring whether genetic polymorphisms in the EGFR gene might predict mobilization capacity of the individual so that therapy can be tailored to those who need it most.

M. A. Ryan et al., Pharmacological inhibition of EGFR signaling enhances G-CSF–induced hematopoietic stem cell mobilization. Nat. Med. 16, 1141–1146 (2010). [Abstract]

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